Results 'fantastic news'

Screening is urged for patients at high risk for the complication

WASHINGTON -- A major international study has found that regular blood transfusions prevent the vast majority of strokes in children with sickle cell disease, doctors said yesterday.

Researchers said they ended the study 16 months early because preliminary results showed that the treatment reduced the risk of stroke by 90 percent in young patients at high risk for the $H debilitating complication, and it would be wrong to limit the therapy to just some patients in the study.

Stroke is a frequent complication among children with sickle cell disease. Screening and treating those most at risk could prevent paralysis, brain damage, learning difficulties and other problems thousands of children afflicted with the inherited blood disorder, experts said.

"This is an important contribution to sickle cell care," said Dr. Robert Adams of the Medical College of Georgia in Augusta, the lead investigator of the trial. "This means we should be able to make a major impact on stroke in children with sickle cell disease."

The National Heart, Lung and Blood Institute of the National Institutes of Health in Bethesda, the sponsor of the trial, issued a clinical alert yesterday to doctors treating children with sickle cell disease, urging them to begin screening patients for those who might be at high risk of stroke and to consider the transfusion therapy as a preventive measure.

"This is very good news for the roughly 2,500 children with sickle cell anemia who may be at risk for stroke, and for their families," said Dr. Claude Lenfant, the director of the institute. "Although this is not a cure, transfusions offer these children the hope of avoiding the devastating consequences of stroke."

Researchers made the announcement in Washington at a national conference commemorating the 25th anniversary of the institutes' Sickle Cell Disease Program, which sponsors much of the nation's research aimed at combating sickle cell anemia and related disorders.

This is the second time in less than three years that a major federal sickle cell treatment study has ended early because of unexpectedly promising results.

In January 1995, researchers halted a national study involving hydroxyurea when it became clear that the drug could reduce the painful crisis episodes characteristic of sickle cell by attacking the underlying cause of the disease.

In the United States, sickle cell disease mainly afflicts African-Americans and people of Hispanic descent, but it is also seen in people of Mediterranean and East Indian descent. The disease occurs when red blood cells contain an abnormal form of hemoglobin, the oxygen-carrying molecules in blood, which can cause them to stiffen and contort into jagged shapes that can block and damage vessels.

The most common form of the disease is sickle cell anemia, which a baby gets by inheriting a sickle hemoglobin gene from both parents, but other forms of sickle disease can result from getting a sickle hemoglobin gene from one parent and a gene for another abnormal hemoglobin from the other.

Experts estimate that more than 70,000 Americans have sickle cell anemia and that about one-third of them are 2 to 16 years old. About 10 percent of children with sickle cell anemia experience strokes, they said, so about 25,000 children will have to be screened to identify the 2,500 at highest risk.

Strokes occur when part of the blood supply to the brain is cut off by restricted vessels or when a blood vessel in the brain breaks, causing tissue to die. A massive stroke can result in death, but a smaller one can produce symptoms such as paralysis, weakened limbs, slurred speech, diminished sight, cognitive defects or learning disabilities.

In general, strokes are far more common in adults than in children. But doctors estimate that there are 3,000 to 5,000 cases of stroke in children each year in this country, with the most common causes being sickle cell disease, leukemia and congenital heart disease.

Dr. Oswaldo Castro, director of the Center for Sickle Cell Disease at Howard University in Washington, said no one knew the exact stroke risk for adults with sickle cell, but it appeared to be less than in children.

"With our adult patients, we see a fair number who show symptoms of earlier strokes, such as paralysis, seizures and other problems," he said.

Castro called results of the children's study "fantastic news," since it showed that it was possible to prevent a first stroke. Those who have a first stroke have more than an 80 percent chance of suffering another if they do not get preventive therapy, he said.

Adams, the neurologist who led the new study, said the regimen for preventing a first stroke was based on earlier observations that stroke patients treated with frequent blood transfusions had a greatly reduced risk of subsequent attacks.

To identify those at high risk of a first stroke, Adams modified a brain-scanning method called transcranial Doppler screening to work with children. This ultrasound technique measures the velocity of blood flow in the brain, with higher flow rates in major arteries indicating narrowed blood vessels that increase the risk of stroke.

For more information on the stroke trial and the clinical alert, doctors can telephone the heart institute's information office at 301-496-4236 or find the institute's Web site at http: //www.nhlbi.nih. gov/nhlbi/nhlbi.htm.